Prostaglandin E₂ Activates NLRP3 Inflammasome in Endothelial Cells to Promote Diabetic Retinopathy

Abstract

Proliferative diabetic retinopathy (PDR) is the leading cause of blindness and accounts for approximately 12% of all new cases of blindness. Prostaglandin E₂ (PGE₂) and nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes have been long considered to be associated with PDR. Levels of pro-inflammatory mediators were examined by Enzyme-linked immunosorbent assay (ELISA) measurements. PGE₂ levels were analyzed by using the Prostaglandin E₂ Monoclonal EIA Kit. Human retinal microvascular endothelial cells (HRMECs) were stained with Annexin V/propidium iodide and analyzed by flow cytometry for testing the apoptosis. Expression levels of NLRP3 inflammasome components under various conditions were detected by Western blot and real-time PCR. Inflammasome markers and PGE₂ were highly expressed in the vitreous of PDR patients. PGE₂ and NLRP3 induced apoptosis of HRMECs. PGE₂ upregulated the expression of NLRP3 inflammasome components and inflammatory chemokines. Knockdown of NLRP3 attenuated the expression of NLRP3 inflammasome components and inhibited the effect of PGE₂. Our results suggest that PGE₂ levels and NLRP3 inflammasome activation are closely related to the pathogenesis of PDR and nonsteroidal anti-inflammatory drugs may have a potential therapeutic effect on PDR.

Key words

proliferative diabetic retinopathy (PDR) - NLRP3 inflammasomes - prostaglandin E2 (PGE2) - apoptosis

• References

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